Regional oxygen tensions in vivo change under certain circumstances. For example at a fracture site and during skeletal unloading, bone cells in vivo experience a significant change in oxygen tension. Evidence suggests bone cell functions may be regulated by the oxygen tension of the environment, which may impact bone remodeling. In the proposed project, we aim to investigate the responses of bone cells to oxygen tensions ranging from 1% to 21%. We will look at the effects on proteins associated with bone remodeling in MC3T3-E1 preosteoblast cells by real time quantitative PCR and protein analysis. We will also investigate hypoxia inducible transcription factors, to determine if they influence the expression of bone remodeling associated proteins using gene silencing techniques. Lastly, we will determine if oxygen tension influences the ability of osteoblast cells to induce osteoclast differentiation and activity using a co-culture system. It is our central hypothesis that reduced oxygen tension promotes bone remodeling by enhanced osteoclastic resorption and osteoblastic bone deposition. The goal is to increase our understanding of the effects of oxygen on bone cells, and ultimately fracture healing and bone loss during disuse. [unreadable] [unreadable]